RU2002102860A - The method of obtaining nitroxyalkyl ethers of naproxen - Google Patents

The method of obtaining nitroxyalkyl ethers of naproxen

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Publication number
RU2002102860A
RU2002102860A RU2002102860/04A RU2002102860A RU2002102860A RU 2002102860 A RU2002102860 A RU 2002102860A RU 2002102860/04 A RU2002102860/04 A RU 2002102860/04A RU 2002102860 A RU2002102860 A RU 2002102860A RU 2002102860 A RU2002102860 A RU 2002102860A
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RU
Russia
Prior art keywords
alkylene
defined above
nitroxyalkyl
carbon atoms
amount
Prior art date
Application number
RU2002102860/04A
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Russian (ru)
Other versions
RU2248348C2 (en
Inventor
Франческа Бенедини
Эрмино ОЛДАНИ
Грациано КАСТАЛДИ
Антонио ТАРКУИНИ
Original Assignee
Никокс С.А.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from IT1999MI001753A external-priority patent/IT1313596B1/en
Application filed by Никокс С.А. filed Critical Никокс С.А.
Publication of RU2002102860A publication Critical patent/RU2002102860A/en
Application granted granted Critical
Publication of RU2248348C2 publication Critical patent/RU2248348C2/en

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Claims (5)

Способ получения нитроксиалкиловых эфиров 2-(S)-(6-метокси-2-нафтил)-пропановой кислоты с энантиомерным избытком, превышающим или равным 97%, предпочтительно превышающим или равным 98%, отличающийся тем, что галогенангидрид 2-(S)-(6-метокси-2-нафтил)-пропановой кислоты формулы А-Hal, где А представляет собой ацильный остаток указанной кислоты, подвергают взаимодействию в инертном органическом растворителе с алифатическим нитроксиалкиловым спиртом HO-Y-ONO2, где Y имеет одно из следующих значений: линейный или необязательно разветвленный C1-C20, предпочтительно С2-С5, алкилен, или циклоалкилен, содержащий в кольце от 3 до 8 атомов углерода, предпочтительно, от 5 до 7 атомов углерода, причем указанный циклоалкилен необязательно замещен одним или двумя алкиленами, определенными выше, и/или одним или более алкильными радикалами, содержащими в цепи такое же число атомов углерода, что и определенный выше алкилен, ароматический остаток, содержащий в кольце 5 или 6 атомов углерода, причем указанный ароматический остаток необязательно замещен одним или двумя алкиленами, определенными выше, и/или одним или более алкильными радикалами, содержащими в цепи такое же число атомов углерода, что и определенный выше алкилен, или группой -СООН;The method of producing nitroxyalkyl esters of 2- (S) - (6-methoxy-2-naphthyl) propanoic acid with an enantiomeric excess of greater than or equal to 97%, preferably greater than or equal to 98%, characterized in that the 2- (S) - halide A (6-methoxy-2-naphthyl) propanoic acid of the formula A-Hal, where A is an acyl residue of the indicated acid, is reacted in an inert organic solvent with an aliphatic nitroxyalkyl alcohol HO-Y-ONO 2 , where Y has one of the following meanings : linear or optionally branched C 1 -C 20 , preferably meaningfully C 2 -C 5 alkylene or cycloalkylene containing from 3 to 8 carbon atoms in the ring, preferably from 5 to 7 carbon atoms, said cycloalkylene optionally substituted with one or two alkylenes as defined above and / or one or more alkyl radicals containing in the chain the same number of carbon atoms as the alkylene defined above, an aromatic residue containing 5 or 6 carbon atoms in the ring, said aromatic residue optionally substituted with one or two alkylene, as defined above, and / or one or more alkyl radicals containing in the chain the same number of carbon atoms as the alkylene defined above, or a —COOH group;
Figure 00000001
Figure 00000001
Figure 00000002
Figure 00000002
 причем Т представляет собой алкилен, определенный выше, и р является целым числом, равным нулю или одному, алкилен имеет вышеупомянутое значение, nf является целым числом от 1 до 6, предпочтительно от 1 до 4, в присутствии неорганического основания и получают соответствующий нитроксиалкиловый эфир 2-(S)-(6-метокси-2-нафтил)-пропановой кислоты формулы A-O-Y-ONO2, где А и Y такие, как определено выше.wherein T is alkylene as defined above, and p is an integer of zero or one, alkylene has the above meaning, nf is an integer of 1 to 6, preferably 1 to 4, in the presence of an inorganic base and the corresponding nitroxyalkyl ether 2 is obtained - (S) - (6-methoxy-2-naphthyl) propanoic acid of the formula AOY-ONO 2 , wherein A and Y are as defined above. 2. Способ по п.1, отличающийся тем, что молярное соотношение количества алифатического нитроксиалкилового спирта с количеством галогенангидрида кислоты составляет в пределах 1-2, предпочтительно 1,2-1,5.2. The method according to claim 1, characterized in that the molar ratio of the amount of aliphatic nitroxyalkyl alcohol to the amount of acid halide is in the range of 1-2, preferably 1.2-1.5. 3. Способ по пп.1 и 2, отличающийся тем, что неорганическими основаниями являются гидроксиды, оксиды, карбонаты и гидрокарбонаты, силикаты, алюмосиликаты щелочных и щелочноземельных металлов или гидроксиды, оксиды, карбонаты и гидрокарбонаты металлов, принадлежащих к группе IIB, предпочтительно, цинка, или к группам IIIa или IVa, предпочтительно, олова.3. The method according to claims 1 and 2, characterized in that the inorganic bases are hydroxides, oxides, carbonates and bicarbonates, silicates, aluminosilicates of alkali and alkaline earth metals or hydroxides, oxides, carbonates and bicarbonates of metals belonging to group IIB, preferably zinc or to groups IIIa or IVa, preferably tin. 4. Способ по пп.1-3, отличающийся тем, что молярное соотношение количества неорганического основания с количеством галогенангидрида кислоты составляет в пределах 1-2, предпочтительно 1,2-1,5.4. The method according to claims 1 to 3, characterized in that the molar ratio of the amount of inorganic base to the amount of acid halide is in the range of 1-2, preferably 1.2-1.5. 5. Способ по пп.1-4, отличающийся тем, что реакцию проводят при температуре в пределах от -20°С до 50°С, предпочтительно от 0 до 20°С.5. The method according to claims 1 to 4, characterized in that the reaction is carried out at a temperature in the range from -20 ° C to 50 ° C, preferably from 0 to 20 ° C.
RU2002102860/04A 1999-08-04 2000-07-27 Method for preparing naproxen nitroxyalkyl esters RU2248348C2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT1999MI001753A IT1313596B1 (en) 1999-08-04 1999-08-04 PROCESS FOR THE PREPARATION OF NITROXIALKYL ESTERS OF NAPROXENE
ITMI99A001753 1999-08-04

Publications (2)

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RU2002102860A true RU2002102860A (en) 2003-09-20
RU2248348C2 RU2248348C2 (en) 2005-03-20

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Country Status (23)

Country Link
US (2) US6700011B1 (en)
EP (2) EP1384707B1 (en)
JP (2) JP4667691B2 (en)
KR (1) KR100687820B1 (en)
CN (1) CN1198786C (en)
AT (2) ATE297372T1 (en)
AU (1) AU778694B2 (en)
BR (1) BRPI0012915B1 (en)
CA (1) CA2380116C (en)
DE (2) DE60020753T2 (en)
DK (2) DK1200386T3 (en)
ES (2) ES2243859T3 (en)
HU (1) HU227109B1 (en)
IL (1) IL147639A0 (en)
IT (1) IT1313596B1 (en)
MX (1) MXPA02001256A (en)
NO (1) NO327669B1 (en)
PL (1) PL200165B1 (en)
PT (2) PT1200386E (en)
RU (1) RU2248348C2 (en)
TR (1) TR200200290T2 (en)
WO (1) WO2001010814A1 (en)
ZA (2) ZA200200478B (en)

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